The direct in vitro conversion of dopamine sulfate to norepinephrine has recently been demonstrated by other investigators. The proposed project will determine if dopamine sulfate is an in vivo precursor for norepinephrine and/or dopamine, or merely a dopamine metabolite, in the Rhesus monkey. A stable isotope of dopamine sulfate will be synthesized, and this compound used to determine kinetic parameters of dopamine sulfate in the Rhesus monkey. These results will be used to design the next experiment. Stable isotopes of dopamine and dopamine sulfate will be infused until steady-state enrichments of these compounds, and of the catecholamines derived from them, are reached and maintained in the blood. Results will be interpreted to provide quantitative answers to each of the following questions: (1) Is dopamine sulfate a direct and/or indirect (via dopamine) precursor of norepinephrine in vivo? (2) Is dopamine sulfate a significant source of free dopamine? (3) Is dopamine sulfate a normal metabolite of dopamine? (4) Does the kidney contribute dopamine or dopamine sulfate to the urine? (5) Does dopamine sulfate enter the cerebrospinal fluid from the blood? Another series of experiments will be conducted to select those tissues or brain areas in Rhesus monkeys and dogs in whic dopamine sulfate metabolic conversions are most likely to occur. Similar studies will be done in control and spontaneously hypertensive rats to help elucidate any role for dopamine sulfate in the development of elevated blood pressure. The results of these studies will broaden our understanding of basic catecholamine synthesis and metabolic mechanisms. If dopamine sulfate is found to be a precursor for norepinephrine or dopamine, these results will have extremely broad implications for our understanding of homeostasis and the many diverse diseases thought to involve the catecholamines. In addition, drug treatment of many of these diseases, including cardiovascular and renal disorders, would almost certainly be improved.